LEUPRORELIN 3-MONTH-DEPOT - A NEW GANLENI CAL FORMULA OF A WELL-ESTABLISHED GNRH ANALOG FOR TREATMENT OF PROSTATE-CANCER

In an open, randomized phase II clinical trial, a total of 27 patients with histologically confirmed advanced or metastatic prostate cancer were treated with the GnRH analogue leuprorelinacetate. The results of an interim analysis of the first 6 months of this ongoing study are p resented. Two different galenical formulas were investigated. Ten pati ents were treated with the 1-month-depot, 17 patients received the new ly developed 3-month-depot containing 3.75 mg and 11.25 mg, respective ly. In both groups, s.c. injections of leuprorelinacetate depot produc ed a complete down-regulation of the pituitary, thus leading to persis tent suppression of testosterone and DHT to castration range (> 50 ng/ dl for testosterone) during the entire observation period. After achie vement of castrate levels, no escape of serum testosterone could be de tected. Parallel to gonadal suppression, a marked reduction of median PSA-levels could be observed leading to a -97.0% (1-month-depot) and - 98.3% (3-month-depot) reduction compared to baseline levels. The major ity of patients showed an objective response to both formulas. During concomitant treatment with cyproteroneacetate for prevention of clinic al tumor flare in a subgroup of 9 patients, slight modifications of se rum testosterone and PSA kinetics during the first month of treatment became obvious. Thereafter no relevant differences could be observed. The 3-month-depot showed a higher meadian peak concentration (C-max) o f leuprorelinacetate (21.60 ng/ml) compared to the 1-month-depot of 9. 79 ng/ml. During the steay state a constant leuprorelin release could be detected leading to median levels in a comparable range for both fo rmulas of 0.28 ng/ml (1-month-depot) and of 0.31 ng/ml (3-month-depot) . t(max) was reached after 1 and 3 hours, respectively. Both galenic f ormulas of the potent GnRH analogue leuprorelinacetate are safe and hi ghly effective for the treatment of prostate cancer, leading to compar able endocrinological effects.